Modulation of Ca(2+)-gated cardiac muscle Ca(2+)-release channel (ryanodine receptor) by mono- and divalent ions.
The effects of mono- and divalent ions on Ca(2+)-gated cardiac muscle Ca(2+)-release channel (ryanodine receptor) activity were examined in [3H]ryanodine-binding measurements. Ca2+ bound with the highest apparent affinity to Ca2+ activation sites in choline chloride medium, followed by KCl, CsCl, NaCl, and LiCl media. The apparent Ca2+ binding affinities of Ca2+ inactivation sites were lower in choline chloride and CsCl media than in LiCl, NaCl, and KCl media. Sr2+ activated the ryanodine receptor with a lower efficacy than Ca2+. Competition studies indicated that Li+, K+, Mg2+, and Ba2+ compete with Ca2+ for Ca2+ activation sites. In 0.125 M KCl medium, the Ca2+ dependence of [3H]ryanodine binding was modified by 5 mM Mg2+ and 5 mM beta,gamma-methyleneadenosine 5'-triphosphate (a nonhydrolyzable ATP analog). The addition of 5 mM glutathione was without appreciable effect. Substitution of Cl- by 2-(N-morpholino)ethanesulfonic acid ion caused an increase in the apparent Ca2+ affinity of the Ca2+ inactivation sites, whereas an increase in KCl concentration had the opposite effect. These results suggest that cardiac muscle ryanodine receptor activity may be regulated by 1) competitive binding of mono- and divalent cations to Ca2+ activation sites, 2) binding of monovalent cations to Ca2+ inactivation sites, and 3) binding of anions to anion regulatory sites.
Liu
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Department of Physiology, University of North Carolina, Chapel Hill 27599-7260, USA.
Pasek
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DA
Meissner
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent / Q000494:pharmacology*; D002414:Cations, Monovalent / Q000494:pharmacology*; D004285:Dogs; D006321:Heart / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D009994:Osmolar Concentration; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000502:physiology*
D002413:Cations, Divalent; D002414:Cations, Monovalent; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002118:Calcium